The long-term objective of this research is to understand how brain[unreadable] cells produce specific behavioral responses. Because lordosis, a[unreadable] component of female reproductive behavior, is strictly dependent on the[unreadable] ovarian steroid hormones estradiol (E2) and progesterone (P),[unreadable] examination of mechanisms that control lordosis allow us to ask how[unreadable] hormonal signals are recognized by brain cells and translated into[unreadable] specific changes in behavior. The research proposed in this application[unreadable] combines behavioral, biochemical, and pharmacological approaches to[unreadable] address specific questions raised by our prior work regarding the neural[unreadable] mechanisms of E2 regulation of lordosis behavior in female rats.[unreadable] [unreadable] Specific Aim 1 uses in vivo microdialysis to test the hypotheses: (1)[unreadable] that somatosensory (flank/perineal and/or vaginocervical) rather than[unreadable] olfactory stimuli associated with copulation are responsible for[unreadable] norepinephrine (NE) release from the hypothalamus of hormone-treated,[unreadable] sexually receptive female rats, and (2) that steroid priming potentiates[unreadable] somatosensory stimulus-evoked NE release. Specific Aim 2 uses[unreadable] biochemical pharmacological approaches to test the hypothesis that E2[unreadable] modifies opioid receptor signaling in the hypothalamus such that[unreadable] pathways inhibitory to lordosis (e.g., mu receptor-linked) are[unreadable] attenuated while pathways that facilitate lordosis (e.g., kappa and[unreadable] delta receptor-linked) are enhanced. Specific Aim 3 tests the[unreadable] hypothesis that the second messenger cGMP and its cellular effectors are[unreadable] hormone-regulated mediators of the facilitatory actions of E2 and P on[unreadable] lordosis behavior in female rats. Neuropharmacological studies will[unreadable] examine whether inhibition of cGMP-dependent protein kinase (PKG)[unreadable] reduces lordosis, and microdialysis studies will evaluate whether there[unreadable] is efflux of cGMP in the hypothalamus during mating tests in hormone-[unreadable] primed female rats. Immunological, biochemical and molecular biological[unreadable] methods will determine whether hormones regulate the expression of[unreadable] guanylyl cyclase, of PKGs, and/or of a specific PKG substrate in brain[unreadable] areas that regulate reproduction. These studies will provide novel[unreadable] insights into the cellular and molecular mechanisms by which ovarian[unreadable] sterioids act in the brain and to produce predictable behavioral[unreadable] changes.